Response of proximal tubules to angiotensin II changes during maturation.
The renin-angiotensin system changes with age, but it is unclear how renal responses to angiotensin II (Ang II) evolve as an animal matures. We hypothesized that Ang II exerts a greater effect on proximal nephron volume absorption (Jv), blood pressure (BP), renal blood flow (RBF), and renal vascular resistance (RVR) in young compared with adult rats. To test this hypothesis, we investigated the effects of Ang II on proximal nephron fluid absorption in response to 10(-10) mol/L Ang II in rats from three age groups: young (4 to 5 weeks old), intermediate (6 weeks old), and adult (7 weeks old). In proximal straight tubules from 7 young rats, Jv was 0.64+/-0.05 nL/mm per minute. Ang II in the bath increased Jv by 69+/-18% to 1.05+/-0.07 nL/mm per minute (P<.005). In tubules from five intermediate-aged rats, Jv was 0.60+/-0.10 nL/mm per minute and increased by 34+/-5% to 0.83+/-0.16 nL/mm per minute after Ang II (P<.02). In five adult rats, Jv was 0.69+/-0.06 nL/mm per minute and increased 20+/-6% to 0.85+/-0.13 nL/mm per minute after Ang II (P<.05). Next we tested whether the exaggerated effect of Ang II on proximal tubular Jv in young rats was due to Ang II-induced changes in cAMP. cAMP content of proximal tubules from eight young rats was 24.8+/-7.6 fmol/mm and fell by 29.7+/-9.8% (P<.025) after treatment with Ang II. In contrast, cAMP content of proximal tubules from nine adults was only 9.8+/-4.5 fmol/mm, 40% of baseline in young rats, and was unchanged by Ang II (9.2+/-4.5 fmol/mm). We finally determined whether the increased sensitivity to Ang II in tubules of young rats is mimicked by renal hemodynamics. Eleven adult rats had BP of 115+/-5 mm Hg, RBF of 6.99+/-0.42 mL/min per g kidney weight (kw), RVR of 16.82+/-0.95 mm Hg/mL per minute per g kw (resistance units), and plasma renin activity (PRA) of 11.2+/-2.3 ng Ang I/mL per hour. Seven young rats had BP of 98+/-7 mm Hg, 17 mm Hg lower than adults (P<.025). RBF was 4.94+/-0.23 mL/min per g kw, and RVR was 20.30+/-1.19 RU, 20% greater than in adults (P<.025). PRA was 9.2+/-2.2 ng Ang I/mL per hour. There were no differences between groups with regard to increased BP, decreased RBF, or increased RVR with graded doses of 8, 40, and 200 fmol Ang II/g body weight. Thus, Ang II increased Jv more in young rats but had a lesser effect in adults. This was coupled with a greater effect of Ang II on tubular cAMP in young rats, but no differences in systemic or renal hemodynamic responses to Ang II between adults and young. We conclude that during adolescent development, Ang II may be an important factor in the regulation of salt and water metabolism, but not renal hemodynamics.
Garvin
J L
JL
Division of Hypertension and Vascular Research, Henry Ford Hospital, Detroit, Mich 48202, USA.
Beierwaltes
W H
WH
D000042:Absorption; D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009399:Nephrons / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000804:Angiotensin II; D000242:Cyclic AMP